GOAL: SYSTEMATIC REVIEW OF CLINICAL COMPLICATIONS OF SICKLE CELL TRAIT (SCT) For Aim 1: A systematic review of published research articles between January 1970 and June 30, 2018 on SCT is in progress. Original research articles that reported an association between SCT and clinical outcomes of interest are reviewed by an expert working group. Each article is rated and the articles outcomes are reviewed for the strength of the evidence. GOAL: EXPLORING THE MICROBIOME AND ENVIRONMENTAL CONTRIBUTIONS TO SICKLE CELL DISEASE AND LEG ULCERS Aim 2: The study of leg ulcers in sickle cell disease is ongoing. As of September 1, 2018, we have recruited 196 participants. We have increased our accrual goal for the skin microbiome study up to 250 participants. We will recruit and sample participants with active ulcers, currently with a healed leg ulcer, and those with no previous history of leg ulcers. Additionally, we will compare a previously published microbiome dataset from diabetic foot ulcers to SCD leg ulcers to identify microbial signatures (similarities or differences) that exist in the microbial communities present in the different ulcers, which may be important in the healing process. Aim 3: We will conduct a cross-sectional study to investigate, resilience, stress, social function, health behaviors, and quality of life indicators for each participant with the goal of identifying environmental (i.e. social, physical, and psychosocial) factors that may impact sickle cell disease and the formation and healing of leg ulcers. Aim 4: We will conduct genomic sequencing to seek to identify the role of genetic modifiers in patients with and without leg ulcers. Specifically, we will conduct whole genome sequencing in the participants to study the genetic factors responsible for variation in leg ulceration in our patient population.